» Articles » PMID: 38559627

Assessing Cardiac Contractility From Single Molecules to Whole Hearts

Overview
Date 2024 Apr 1
PMID 38559627
Authors
Affiliations
Soon will be listed here.
Abstract

Fundamentally, the heart needs to generate sufficient force and power output to dynamically meet the needs of the body. Cardiomyocytes contain specialized structures referred to as sarcomeres that power and regulate contraction. Disruption of sarcomeric function or regulation impairs contractility and leads to cardiomyopathies and heart failure. Basic, translational, and clinical studies have adapted numerous methods to assess cardiac contraction in a variety of pathophysiological contexts. These tools measure aspects of cardiac contraction at different scales ranging from single molecules to whole organisms. Moreover, these studies have revealed new pathogenic mechanisms of heart disease leading to the development of novel therapies targeting contractility. In this review, the authors explore the breadth of tools available for studying cardiac contractile function across scales, discuss their strengths and limitations, highlight new insights into cardiac physiology and pathophysiology, and describe how these insights can be harnessed for therapeutic candidate development and translational.

Citing Articles

Dilated cardiomyopathy-associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility.

Garg A, Jansen S, Greenberg L, Zhang R, Lavine K, Greenberg M Proc Natl Acad Sci U S A. 2024; 121(46):e2405020121.

PMID: 39503885 PMC: 11572969. DOI: 10.1073/pnas.2405020121.

References
1.
Bhattacharjee P, Dasgupta D, Sengupta K . DCM associated LMNA mutations cause distortions in lamina structure and assembly. Biochim Biophys Acta Gen Subj. 2017; 1861(11 Pt A):2598-2608. DOI: 10.1016/j.bbagen.2017.08.016. View

2.
Morgan B, Muci A, Lu P, Qian X, Tochimoto T, Smith W . Discovery of omecamtiv mecarbil the first, selective, small molecule activator of cardiac Myosin. ACS Med Chem Lett. 2014; 1(9):472-7. PMC: 4007828. DOI: 10.1021/ml100138q. View

3.
Greenberg M, Tardiff J . Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine. J Gen Physiol. 2021; 153(3). PMC: 7852459. DOI: 10.1085/jgp.202012662. View

4.
Campbell K, Janssen P, Campbell S . Force-Dependent Recruitment from the Myosin Off State Contributes to Length-Dependent Activation. Biophys J. 2018; 115(3):543-553. PMC: 6084639. DOI: 10.1016/j.bpj.2018.07.006. View

5.
Ho C, Sweitzer N, McDonough B, Maron B, Casey S, Seidman J . Assessment of diastolic function with Doppler tissue imaging to predict genotype in preclinical hypertrophic cardiomyopathy. Circulation. 2002; 105(25):2992-7. DOI: 10.1161/01.cir.0000019070.70491.6d. View